There is a fundamental knowledge gap about how the human brain controls one of the most fundamental hand actions, grasping. Developing solutions for the manual impairments that ensue from brain injuries and neurological diseases hinges on closing this knowledge gap. The long-term goal is to determine how cortical and subcortical structures in the brain integrate sensory information into accurate hand actions. The objective of this proposal, which is a stepping-stone towards the long-term goal, is to determine the functional organizations of the parietal-frontal pathways that mediate grasping in monkeys. The central hypothesis is that three parietal-frontal pathways control successive stages of grasping (approach, contact, lift). Each pathway node is further organized into modules that are specific to grip posture (precision and whole hand). This hypothesis has been formulated primarily from studies conducted during the applicant's postdoctoral work. The rationale for the proposed research is that it will close a pressing knowledge gap about how a parietal-frontal networks controls one of the most sophisticated and clinically relevant motor functions. Two specific aims will be pursued to test this hypothesis: (1) Determine how the parietal-frontal pathways control successive stages of grasping; and (2) Determine how modules within nodes of the parietal-frontal pathways encode grip posture. Under the first aim (K-99 phase), optical imaging will be used to identify the parietal and frontal nodes on the cortical surface that are activated during grasping. Electrophysiological recordings in each node identified with optical imaging will be used to determine the relationships between spike train modulations and grasping stages. Under the second aim (R-00 phase), optical imaging and electrophysiological recordings from modules of the same network nodes will show the spatial organizations of clusters of neurons tuned to specific grip postures. Electrical stimulation of the same modules during grasping will be used to temporarily manipulate its mechanisms and further test the contributions of individual modules to grasping. The functional connections of individual modules will be tested with concurrent electrical stimulation and optical imaging, which has already been proven feasible in the applicant's hands. The chief innovation of this proposal is the use of a multi- pronged approach that centers on optical imaging in behaving monkeys to determine how the parietal-frontal network controls grasping. The proposed research is significant because it is expected to vertically expand the understanding of how the parietal-frontal network in the primate brain controls grasping. Ultimately, such knowledge has the potential to advance the design of brain-machine interfaces that rely on recording neuronal signals from the brain to aid hand use for patients who have lost the ability to use their hands due to central nervous system injury or amputation.